Objective To explore the effect and mechanism of remifentanil (RF) on hippocampal neuronal pyroptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD) based on the nod-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway.

Methods A total of 100 neonatal rats were randomly divided into sham-operation group (18 rats) and model group (82 rats). The model group was used to establish the HIBD model using the Rice method, and 72 successfully modeled rats were randomly divided into HIBD group, low-dose RF group, high-dose RF group, and high-dose RF+NLRP3 activator group, with 18 rats in each group. The Longa scoring method was used to evaluate the neurological deficit status of rats in each group; the ratio of wet weight to dry weight (W/D) of brain tissue in each group was detected; the pathological changes in the hippocampal region of rats in each group were observed through hematoxylin-eosin (HE) staining; TUNEL staining and Caspase-1 immunofluorescence double staining were used to detect the pyroptosis of hippocampal neurons in rats in each group; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the hippocampal tissue of rats in each group; Western blot was used to detect the expression of proteins related to the NLRP3/Caspase-1/GSDMD pathway in the hippocampal tissue of rats in each group.

Results The Longa score, W/D in brain tissue, and hippocampal neuronal pyroptosis rate in the HIBD group were all higher than those in the sham-operation group; those in the low-dose RF group and the high-dose RF group were lower than those in the HIBD group; those in the high-dose RF group were lower than those in the low-dose RF group; and those in the high-dose RF+NLRP3 activator group were higher than those in the high-dose RF group, with statistically significant differences (P < 0.05). The levels of IL-6, TNF-α, and IL-1β in the hippocampal tissue of the HIBD group were all higher than those in the sham-operation group; those in the low-dose RF group and the high-dose RF group were lower than those in the HIBD group; those in the high-dose RF group were lower than those in the low-dose RF group; and those in the high-dose RF+NLRP3 activator group were higher than those in the high-dose RF group, with statistically significant differences (P < 0.05). The protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Caspase-1, GSDMD, and the N-terminal fragment of gasdermin D (GSDMD-N) in the hippocampal tissue of rats in the HIBD group were all higher than those in the sham-operation group; those in the low-dose RF group and the high-dose RF group were lower than those in the HIBD group; those in the high-dose RF group were lower than those in the low-dose RF group; and those in the high-dose RF+NLRP3 activator group were higher than those in the high-dose RF group, with statistically significant differences (P < 0.05).

Conclusion RF can alleviate hippocampal neuronal pyroptosis in neonatal rats with HIBD by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway, which may provide a new strategy for perioperative brain protection in neonates.